A model for demonstration of reversal of impairment of endothelium-dependent relaxation in the cholesterol-fed rabbit

Abstract

This investigation was undertaken to determine whether it was possible to restore endothelium-dependent relaxation (EDR) in the cholesterol-fed rabbit model of atherosclerosis following discontinuation of the cholesterol. New Zealand white rabbits, approximately 8 weeks of age, were randomized into (i) control group (9 animals fed a standard rabbit diet) and (ii) experimental group (27 animals: fed the same diet supplemented with 2.5% cholesterol). The experimental animals were restored to the standard diet after 3 weeks. EDR to acetylcholine (−9.0 to −5.0 log mol/L) was examined in the experimental animals at 3, 7, and 15 weeks after commencement of the study (n = 9 at each stage) and the nine control animals examined after 7 weeks. At the end of 7 weeks, EDR to acetylcholine (−6.0 log mol/L) was significantly (p < 0.05) impaired in the experimental group (34.3 ± 3.8%) compared with that in the control group (79.8 ± 3.0%). The loss of EDR was not apparent in the experimental group at 3 weeks (relaxation: 81.7 ± 4.7%). At the end of 15 weeks, the EDR was significantly restored in the experimental group (relaxation: 63.6 ± 5.1%). These findings demonstrate that it is possible to reverse the loss of EDR that occurs with cholesterol feeding in the rabbit by limiting the period of exposure to a high cholesterol diet.Key words: atherosclerosis, endothelium-dependent relaxation, rabbit aorta, regression.